Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the United States, accounting for 30,000 deaths yearly in the United States (Jemal et al. 2009). Pancreatic cancer is characterized by a rapid disease progression and absence of specific symptoms, largely precluding an early diagnosis and meaningful treatment (Stathis & Moore, 2010; Schneider et al. 2005).
Despite aggressive efforts to improve treatment for patients with pancreatic cancer, limited progress has been made (Stathis & Moore 2010; Pancreatic Cancer UK 2011). Although improvement is being made through the development of improved targeted and systemic therapies, the prognosis and treatment of pancreatic cancer is still inadequate. This is due both to the late presentation and the lack of an effective treatment strategy (Li et al. 2004). As a result, gemcitabine as a single agent given postoperatively remains the current standard of care. Combinations with other chemotherapeutic drugs or biological agents given as a palliative setting for unresectable pancreatic cancer or adjuvant setting following resection have resulted in limited improvement (Klinkenbijl et al. 1999; Neoptolemus et al. 2004; Oettle et al. 2007). The 5 yr survival of patients with pancreatic cancer, despite numerous phase 3 trials, remains less than 5% after resection (Vincent et al. 2011; Alexakis 2004; Ghaneh 2007, BSG 2005). The majority of patients will present with either local or systemic recurrence within 2 years following resection and postoperative adjuvant chemotherapy (Vincent et al. 2011; Alexakis 2004; Ghaneh 2007). Currently, the most effective single agent gemcitabine achieves an improved 1-year survival rate from 16 to 19%. Treatment with conventional treatments such as gemcitabine or 5-flurouracil (5-FU) results in a median survival of just a few months (Saif 2009; Rivera et al. 2009). The addition of Tarceva® (erlotinib) in a randomized study added a median of 11 days to overall survival (Cunningham 2009; Heinemann 2012).
This limitation of conventional treatment is due to the profound resistance of PDAC cells towards anti-cancer drugs emerging from the efficient protection against chemotherapeutic drugs (Wong & Lemoine 2009; Fulda 2009). Therefore, it is important to develop new therapeutic strategies for this devastating disease.